Cancer chemoprevention is a promising approach to fighting cancers. However, current methods to evaluate treatment efficacy, in order to identify new and promising chemopreventive agents/regimes, largely depend on invasive tissue biopsy or later endpoints (e.g., reduction of tumor incidence or size). Current methods entail significant distress to patients or require a long term clinical trial. It is particularly difficult to use these approaches for early, timely, and frequent evaluation during the chemoprevention treatment period. Our recent studies indicate that a newly-developed optic imaging technology has great potential for real-time, noninvasive cancer detection by observing subtle alterations in the nuclear morphology of epithelial cells. This technology has never been applied to cancer chemoprevention. In this proposed study, our hypothesis is that the treatment efficacy and response to oral cancer chemoprevention can be monitored and predicted with nuclear imaging prior to invasive tissue biopsy or tumor incidence outcome obtained at the end of the i treatment. We will test our hypothesis in the cheek pouches of a hamster model by establishing tissue "imaging grading" and then predicting the efficacy of retinoid acid chemoprevention. Our specific aims are (1) to characterize and refine this imaging technique by comparing the imaging data with subsequent tissue biopsy results from different developmental stages of oral premalignant lesions to establish nuclear imaging grading; and (2) to determine the capacity of this imaging for noninvasive evaluation and predication of treatment efficacy before the end of a 7-week course of oral cancer chemoprevention with retinoic acid. This is the first study to establish such epithelial imaging classification and use the imaging findings for monitoring and predication of cancer chemoprevention. This proposed study, if successful, will provide an ideal objective tool for treatment monitoring during cancer chemoprevention that will have significant impact on future development of new and improved cancer chemoprevention agents and strategies. [unreadable] [unreadable]